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At least 73 records · Page 4Linked to original sources
PubMed1989

Effect of esters of succinic acid and other citric acid cycle intermediates on insulin release and inositol phosphate formation by pancreatic islets.

Esters of carboxylic acids are permeable to cells and once inside the cell are hydrolyzed to carboxylic acids. Methyl and ethyl esters of succinate and other citric acid cycle intermediates were tested to find out whether they are insulin secretagogues. Monomethyl succinate stimulated insulin release from pancreatic islets in a concentration-dependent manner with maximal release attained at a concentration of 10 mM. Dimethyl succinate (10 mM) was as effective as monomethyl succinate, but pyruvate methyl ester, monoethyl succinate, and dimethyl fumarate were ineffective as primary secretagogues. However, dimethyl fumarate potentiated both leucine- and leucine-plus-glutamine-induced insulin release. Glucose, leucine, leucine plus glutamine, and monomethyl succinate increased inositol tris-, bis- and monophosphate formation in pancreatic islets and antimycin A inhibited this formation. Since mitochondrial metabolism is probably essential for glucose-induced insulin release and the metabolism of succinate and leucine (without or with glutamine) involves mitochondrial respiration exclusively, these results might indicate that mitochondrial metabolism generates conditions or factors that are transmitted to the cytosol to increase inositol trisphosphate formation and thus calcium mobilization and insulin release. Since succinate is believed to enter metabolism at site II of the mitochondrial respiratory chain, it is interesting that rotenone, an inhibitor of NADH dehydrogenase and site I of the respiratory chain, was a potent inhibitor of monomethyl succinate-induced insulin released. Rotenone also inhibited leucine (plus or minus glutamine)-induced insulin release. These results indicate that beta cell metabolism of monomethyl succinate and leucine, like glucose, influences dehydrogenases that produce NADH.

Animals↗
PubMed1972

Use of tartaric acid isomers and citric acid in the biotyping of Salmonella typhimurium.

The colour-change and lead acetate tests for fermentation of d-, l- and m-tartaric acids and citric acid used in the Kristensen scheme for biotyping Salmonella typhimurium were found to be unreliable because, whatever the conditions of culture, they gave different results in replicate tests of the same strains. Many genotypically non-fermenting strains gave inconsistent reactions due to the emergence of fermenting mutant bacilli in some of their test cultures. No reliable test was found for the fermentation of citric acid.A ;turbidity' test was found to give consistent and reliable results with the three tartaric acid isomers. It demonstrated fermentation by the significantly greater amount of growth obtained in a 24 hr. culture in Oxoid peptone water with added isomer than in a control culture without isomer. Lewis & Stocker's (1971) plateinhibition test for fermentation of m-tartrate, which identifies m-tartrate-negative strains because m-tartrate inhibits their growth on citrate- or glycerol-containing minimal medium, was found to be as reliable as, and easier to read than, the turbidity test.Use of the turbidity test for d- and l-tartrates and the plate-inhibition test for m-tartrate in biotyping 1435 strains of S. typhimurium showed that many strains had previously been mistyped by the lead acetate test and distinguished 16 new biotypes in addition to the 22 biotypes already recognized.

Bacteriological Techniques↗
PubMed2002

Simultaneous and direct determination of oxalic acid, tartaric acid, malic acid, vitamin C, citric acid, and succinic acid in Fructus mume by reversed-phase high-performance liquid chromatography.

A method for the simultaneous separation and direct determination of oxalic acid (OA), tartaric acid (TA), malic acid (MA), vitamin C (VC), citric acid (CA), and succinic acid (SA) in Fructus mume using reversed-phase high-performance liquid chromatography with a UV detector in an acidic medium is presented in this study. In the experiment, the optimization of chromatographic conditions (i.e., the pH and flow rate of the mobile phase, the absorption wavelength, and temperature of column) that affect the separation degree and peak shape of organic acids has been obtained. The linear ranges are found to be 0.05-4.7 microg for OA (r = 0.9999), 0.11-10.5 microg for TA (r = 0.9999), 0.114-11.4 microg for MA (r = 0.9999), 0.033-3.30 microg for VC (r = 0.9999), 0.155-15.5 microg for CA (r = 0.9998), and 0.194-19.4 microg for SA (r = 0.9996). For OA, TA, MA, VC, CA, and SA, the even recovery (n = 3) of six effective components are 100.9%, 99.97%, 101.2%, 102.1%, 101.1%, and 100.7%, respectively, and the largest relative standard deviation (n = 11) for the six components is less than 1.7%. The detection limits are 0.01 microg for OA, TA, and VC; 0.05 microg for MA; 0.03 microg for CA; and 0.1 microg for SA. In a single chromatographic run, OA, TA, MA, VC, CA, and SA can be determined in less than 7 min. The method can be used for the purpose of routine analysis and the quality control of a botanic (Fructus mume) containing these effective components.

Ascorbic Acid↗
PubMed1979

Manganese deficiency leads to elevated amino acid pools in citric acid accumulating Aspergillus niger.

Free amino acid pools have been investigated in a citric acid accumulating strain of Aspergillus niger during batch growth under manganese sufficient and deficient conditions by means of an improved chromatographic method. Studies on the mycelial content of several nitrogenous compounds under manganese sufficient and deficient conditions showed that manganese deficiency resulted in lower amino acid pool sizes during trophophase and considerable accumulation during idiophase, and in a reduction of the protein and nucleic acid contents. Addition of cycloheximide to mycelia grown with sufficient manganese also caused an elevation of free amino acid pool sizes, thus indicating that impairment of protein synthesis by manganese deficiency is responsible for the observed rise in amino acid concentration. Furthermore it was observed that the manganese deficient mycelia excreted high amounts of all amino acids suggesting that manganese deficiency may also affect membrane permeability.

Amino Acids↗
PubMed2000

Metabolism of citric acid production by Aspergillus niger: model definition, steady-state analysis and constrained optimization of citric acid production rate.

In an attempt to provide a rational basis for the optimization of citric acid production by A. niger, we developed a mathematical model of the metabolism of this filamentous fungus when in conditions of citric acid accumulation. The present model is based in a previous one, but extended with the inclusion of new metabolic processes and updated with currently available kinetic data. Among the different alternatives to represent the system behavior we have chosen the S-system representation within power-law formalism. This type of representation allows us to verify not only the ability of the model to exhibit a stable steady state of the integrated system but also the robustness and quality of the representation. The model analysis is shown to be self-consistent, with a stable steady state, and in good agreement with experimental evidence. Moreover, the model representation is sufficiently robust, as indicated by sensitivity and steady-state and dynamic analyses. From the steady-state results we concluded that the range of accuracy of the S-system representation is wide enough to model realistic deviations from the nominal steady state. The dynamic analysis indicated a reasonable response time, which provided further indication that the model is adequate. The extensive assessment of the reliability and quality of the model put us in a position to address questions of optimization of the system with respect to increased citrate production. We carried out the constrained optimization of A. niger metabolism with the goal of predicting an enzyme activity profile yielding the maximum rate of citrate production, while, at the same time, keeping all enzyme activities within predetermined, physiologically acceptable ranges. The optimization is based on a method described and tested elsewhere that utilizes the fact that the S-system representation of a metabolic system becomes linear at steady state, which allows application of linear programming techniques. Our results show that: (i) while the present profile of enzyme activities in A. niger at idiophase steady state yields high rates of citric acid production, it still leaves room for changes and suggests possible optimization of the activity profile to over five times the basal rate synthesis; (ii) when the total enzyme concentration is allowed to double its basal value, the citric acid production rate can be increased by more than 12-fold, and even larger values can be attained if the total enzyme concentration is allowed to increase even more (up to 50-fold when the total enzyme concentration may rise up to 10-fold the basal value); and (iii) the systematic search of the best combination of subsets of enzymes shows that, under all conditions assayed, a minimum of 13 enzymes need be modified if significant increases in citric acid are to be obtained. This implies that improvements by single enzyme modulation are unlikely, which is in agreement with the findings of some investigators in this and other fields.

Aspergillus niger↗
PubMed1975

Regulation of the dicarboxylic acid part of the citric acid cycle in Bacillus subtilis.

The regulation of alpha-ketogluterate dehydrogenase, succinate dehydrogenase, fumarase, malate dehydrogenase, and malic enzyme has been studied in Bacillus subitilis. The levels of these enzymes increase rapidly during late exponential phase in a complex medium and are maximal 1 to 2 h after the onset of sporulation. Regulation of enzyme synthesis has been studied in the wild type and different citric acid cycle mutants by adding various metabolites to the growth medium. Alpha-ketoglutarate dehydrogenase is induced by glutamate or alpha-ketoglutarate; succinate dehydrogenase is repressed by malate; and fumarase and malic enzyme are induced by fumarate and malate, respectively. The addition of glucose leads to repression of the citric acid cycle enzymes whereas the level of malic enzyme is unaffected. Studies on the control of enzyme activities in vitro have shown that alpha-ketoglutarate dehydrogenase and succinate dehydrogenase are inhibited by oxalacetate. Enzyme activities are also influenced by the energy level, expressed as the energy charge of the adenylate pool. Isocitrate dehydrogenase, alpha-ketoglutarate dehydrogenase, succinate dehydrogenase, and malic enzyme are inhibited at high energy charge values, whereas malate dehydrogenase is inhibited at low energy charge. A survey of the regulation of the citric acid cycle in B.subtilis, based on the present work and previously reported results, is presented and discussed.

Adenine Nucleotides↗
PubMed2001

The biochemistry of citric acid accumulation by Aspergillus niger.

Fungi, in particular Aspergilli, are well known for their potential to overproduce a variety of organic acids. These microorganisms have an intrinsic ability to accumulate these substances and it is generally believed that this provides the fungi with an ecological advantage, since they grow rather well at pH 3 to 5, while some species even tolerate pH values as low as 1.5. Organic acid production can be stimulated and in a number of cases conditions have been found that result in almost quantitative conversion of carbon substrate into acid. This is exploited in large-scale production of a number of organic acids like citric-, gluconic- and itaconic acid. Both in production volume as well as in knowledge available, citrate is by far the major organic acid. Citric acid (2-hydroxy-propane-1,2,3-tricarboxylic acid) is a true bulk product with an estimated global production of over 900 thousand tons in the year 2000. Till the beginning of the 20th century, it was exclusively extracted from lemons. Since the global market was dominated by an Italian cartel, other means of production were sought. Chemical synthesis was possible, but not suitable due to expensive raw materials and a complicated process with low yield. The discovery of citrate accumulation by Aspergillus niger led to a rapid development of a fermentation process, which only a decade later accounted for a large part of the global production. The application of citric acid is based on three of its properties: (1) acidity and buffer capacity, (2) taste and flavour, and (3) chelation of metal ions. Because of its three acid groups with pKa values of 3.1, 4.7 and 6.4, citrate is able to produce a very low pH in solution, but is also useful as a buffer over a broad range of pH values (2 to 7). Citric acid has a pleasant acid taste which leaves little aftertaste. It sometimes enhances flavour, but is also able to mask sweetness, such as the aspartame taste in diet beverages. Chelation of metal ions is a very important property that has led to applications such as antioxidant and preservative. Moreover, it is a "natural" substance and fully biodegradable.

Aspergillus niger↗
PubMed1982

Effect of amino acids on microbial production of citric acid by Aspergillus niger.

The effect of different concentrations of cysteine, serine, lysine, aspartic acid, and glutamic acid on the growth and fermenting activity of Aspergillus niger AL 29 was studied at different incubation periods. It was observed that the presence of glutamic acid and aspartic acid stimulated the citric acid production to the extent of 79.6% and 76.7%, respectively. Lysine was effective in producing citric acid by 62%. However, serine could not influence the yield (50.4%) to a greater extent, while the effect of cysteine was found to be detrimental. The yield of citric acid was determined on sugar consumption basis.

Amino Acids↗
PubMed1977

Lack of effect of ascorbic and citric acids on calcium metabolism of chickens.

Five experiments were carried out in which various levels of calcium and ascorbic acid or citric acid were fed to adult male chickens, young chickens, or young coturnix. Observations were made on body weight, feed efficiency, plasma calcium and tibia mineral content. One percent dietary ascorbic acid had no adverse effect on body weight, tibia ash or tibia calcium content of adult male chickens over a 224-day period, even at calcium levels as low as 0.026% of the diet. In growing chicks, body weight and plasma calcium and tibia mineral content varied with the calcium level of the diet, but were not influenced by ascorbic acid even at 0.65% of the diet. Citric acid at the same molar level was also ineffective in altering calcium metabolism in growing chickens. Growing coturnix showed differences in growth and tibia ash content with 0.4% and 0.85% calcium, but there were no pronounced effects caused by dietary ascorbic acid. There is no evidence in this work that these relatively high levels of ascorbic acid or citric acid have any adverse effect on calcium metabolism because of their chelating properties.

Animals↗
PubMed2001

[Determination method of isocitric acid in food additive citric acid].

A simple and rapid method using HPLC was developed for the determination of isocitric acid in food additive citric acid. One gram of sample was dissolved in 100 mL of water. HPLC separation was performed on an Inertsil ODS-3 column (4.6 mm i.d. x 250 mm) using 0.1% phosphoric acid as the mobile phase at a flow rate of 1 mL/min. Isocitric acid was detected at 210 nm. The calibration graph was rectilinear from 5 to 100 micrograms/mL. The recoveries of isocitric acid from sample at the levels of 0.1% and 0.4% were 98% and 99%, respectively, and the determination limit was 0.05%.

Chromatography, High Pressure Liquid↗
PubMed1984

The pulpal response to citric acid in cats.

Citric acid conditioning of dentine has been proposed as an efficacious treatment for promoting re-attachment after periodontal surgery. This study investigated the pulpal reactions to periodontal surgery combined with citric acid (pH 1) demineralization of exposed dentine for 3 min. 9 cats were used as the experimental animals, with each cat providing 1 negative and 1 positive control and 2 experimental canine teeth. Evaluation was over 3 observation periods, with 3 cats in each period being sacrificed at 4, 21 and 83 days. Positive control teeth, which underwent periodontal surgery combining the removal of approximately 3 mm2 of labial bone and vigorous root planning of the exposed root surfaces, displayed mild to moderate pulpal reactions during the short- and intermediate-term periods and only mild to no reactions in the long-term period. The addition of citric acid demineralization, however, resulted in 5 experimental teeth (28%) becoming abscessed or totally necrotic in the intermediate- and long-term periods. At 21 days, the frequency of adverse pulpal responses to surgery and citric acid conditioning was significantly (p less than 0.05) greater than to surgery alone. Although 4 experimental teeth were relatively uninflamed at the long-term period of observation, all showed irritational dentine formation. Penetration of exposed dentinal tubules by plaque bacteria was observed only in the citric acid treated teeth.

Acid Etching, Dental↗